Disruption of sphingolipid biosynthetic gene IPT1 reduces Candida albicans adhesion and prevents activation of human gingival epithelial cell innate immune defense.
Med Mycol
; 49(5): 458-66, 2011 Jul.
Article
em En
| MEDLINE
| ID: mdl-21091155
ABSTRACT
We demonstrated the effect of a Candida albicans sphingolipid biosynthetic gene, IPT1, on the interaction between gingival epithelial and Candida cells using monolayer cultures and engineered human oral mucosa tissue (EHOM). Disrupting the IPT1 gene greatly reduced Candida adhesion to gingival epithelial cells, compared to the wild-type and revertant strains. The yeasts adhesion to epithelial cells may activate toll-like receptors (TLRs). Cell response against Candida infection was thus investigated by evaluating TLR expression and antimicrobial peptide (AMP) production. The wild-type and revertant strains both activated TLR2, TLR4, TLR6, and TLR9 gene expression in the epithelial cells, whereas the Δipt1 mutant Candida strain had no effect on this expression. This finding was supported by an increased AMP expression (human ß-defensin HBD-2 and HBD-3) in the EHOM tissue infected with the wild-type and revertant Candida strains, and a decreased expression in the Δipt1 mutant-infected model. HBD protein secretion confirmed the absence of any effect by the Δipt1 on epithelial cell innate defense. This is the first study to demonstrate that a disruption of the IPT1 gene affects Candida-host interaction, thus preventing TLR activation and ß-defensin expression.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Candida albicans
/
Proteínas Fúngicas
/
Adesão Celular
/
Peptídeos Catiônicos Antimicrobianos
/
Fatores de Virulência
/
Células Epiteliais
/
Receptores Toll-Like
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Med Mycol
Assunto da revista:
MEDICINA VETERINARIA
/
MICROBIOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Canadá